Porphyrin, a tetrapyrrolic macrocycle, is the active component of many naturally occurring pigments and has been known and studied for centuries; its biological importance can hardly be overestimated. In spite of this ubiquity, it was only in 1966 that the first expanded porphyrin analogue, sapphyrin, was reported and it has only been in recent years that the area of expanded porphyrin research has begun to attract attention as its own rapidly evolving field. One of the unexpected surprises to emerge from this work is the finding that large expanded porphyrins, those containing 6 to 8 or more pyrroles, are often not flat but rather adopt “figure eight” and other twisted conformations in spite of being highly conjugated. Because of this, it remains a challenge at present to produce large aromatic expanded porphyrins that display the classic disk-like structure of simple porphyrins.
One approach to obtaining large, flat expanded porphyrins is to invert one or more of the pyrrolic rings such that a compound lacking the classic “all-NH-in” structure of porphyrins is produced. To date, however, the preparation of higher order fused oligopyrrolic systems, including α-α′ unsubstituted quaterpyrroles, has proved elusive. For a summary of expanded porphyrins and their heterologs, see Jasat A. and D. Dolphin in Chemical Reviews, 1997, Vol 97:6, 2267-2340. Cyclo[n]thiophenes (with n=12, 16, 18) have been reportedly synthesized. In spite of their 4n π-electron conjugation pathways, these systems did not display much in the way of obvious ring current effects (J. Krömer, et al., Angew. Chem. 2000, 112, 3481; Angew. Chem. Int. Ed. Engl. 2000, 39, 3481). The synthesis strategy used is limited to rings having at least 12 members, and all nitrogen-containing macrocycles are not possible using the cyclo[n]thiophene synthesis method.
The present invention also relates to complexation and recognition of anions. Anions play essential roles in biological processes; indeed, it is believed that they participate in 70% of all enzymatic reactions. A number of research groups have followed Nature's lead and have designed and synthesized receptors that use hydrogen bonds alone, or in concert with electrostatic interactions, to coordinate to anions. Nonetheless, there remains at present a critical need for additional anion complexing agents that are either easy to make or inherently selective in their substrate binding properties. Current technology for dialysis in medical applications relies on membranes, such as microfiltering cellophane, to filter anions such as chloride anion or phosphate-containing anions from the blood stream. Aluminum hydroxide or calcium carbonate cocktails must be consumed by the dialysis patient in order to bind the anionic species. A major drawback of this technology is that aluminum builds up in cellular membranes to toxic levels over time causing ailments including dementia and death. Calcium carbonate offers a less toxic substitute, however, it is less efficient and is associated with hypercalcemia.
Water-soluble anion binding agents are desired as drug delivery agents. For example, many anti-viral drugs only show activity when phosphorylated. However, many phosphorylated drug derivatives are too polar to pass through cell wall membranes. A water-soluble anion binding agent may be able to encapsulate the negative charge and so allow the drug to pass through cell walls. The synthesis of new molecular devices designed to sense and report the presence of a particular substrate is an area of analytical chemistry that is attracting attention. The detection of anionic species is a particular challenge, as anions are difficult to bind and are generally larger than cations leading to a smaller charge-to-radius ratio. Sensors that allow for the detection of biologically important anions such as chloride, phosphate, sulphate, and fluoride via colorimetric or spectroscopic means without interference from endogenous chromophores would be particularly useful in the area of medical analysis. The present invention relates to the development of such sensors.
The present invention also relates to cation binding agents useful as sensors for particular cations or as sequestering agents. Particular cation-complexes may be useful in medicine as imaging agents or in the treatment of disease.
Currently, the ability to translate, amplify, and direct digital traffic depends in part on nonlinear optical (NLO) materials. Thus, materials with nonlinear optical properties are valued as optical switches in fiberoptic communications systems. The most popular NLO materials have been brittle ceramics, such as LiNbO3. Organic materials that could be poured or molded into a shape, such as polymers, would offer advantages such as exceptional optical qualities, low cost, and ease of fabrication into device structures. Such materials could include molecular fragments displaying NLO activity, or highly colored chromophores, dissolved in or covalently attached to a polymeric host material or incorporated into liquid crystals. A material suitable for widespread industrial use has yet to be synthesized, however.
The present invention also relates to optical filters, particularly, infrared filters. New materials are needed that possess absorption in the infrared range while displaying transparent properties in the visible range.
The present inventors addressed the problem of producing large aromatic expanded porphyrins that display the classic disk-like structure of simple porphyrins and provide herein novel molecules that possess such disk-like structures as well as properties that address unmet needs in areas cited above.